The phthalazinone derivative azelastin (INN) has been successfully used in the treatment and prophylaxis of bronchial asthma and allergic and seasonal rhinitis. It can be synthesized as described in German patent 2 164 058.
D-18024 hydrochloride (INN: flezelastin) was developed as a follow-up preparation in the form of the racemic mixture. The method of preparation is described in European patent 222 191.
It has now surprisingly been found that the phthalazinone derivatives of the general formula I ##STR1## where A=phenyl (unsubstituted, mono- or multi-halogen substituted), H or C.sub.1 -C.sub.3 -alkyl, 2-furyl or 2-thienyl and ##STR2## with Y.dbd.H or C.sub.1 -C.sub.6 -alkyl, where the alkyl radical can be substituted with a (substituted) phenyl ring, a hydroxy group or an alkoxycarbonyl group as well as all physiological acceptable acid addition salts thereof and in particular the compounds of Formula II, III, IV ##STR3## as well as the optical isomers of azelastin and the optical isomers of flezelastin--have an antiarrhythmic effect. They can presumably be classified in the group of Class III-antiarrhythmically acting compounds.
The compounds also have an analgesic activity.
The compounds of the invention also have an anti-emetic effect. The anti-emetic effect has been found by inhibition of cisplatinum-induced emesis in awake domestic pigs after oral or intravenous administration.
______________________________________ Inhibition of cisplatinum-induced emesis in awake domestic pigs. The data represent the number of emetic attacks during the observation period. The values given are means of 5 individual Time 0-24 Compound Dose 0-4 Hours 0-8 Hours Hours ______________________________________ Control 10 10 12 i.v. 5 mg/pig 8 9 18 15 mg/pig 0 3 11 50 mg/pig 0 0 2 p.o. 10 mg/pig 3 3 3 25 mg/pig 0 0 3 60 mg/pig 0 1 2 100 mg/pig 0 0 1 200 mg/pig 0 0 0 ______________________________________
The compounds of Formula I are prepared by the method of German patent DE 2 164 058, the compound according to Formula II by analogy with the instructions contained in German patent 2 164 058, Example 10. The compound of Formula III is prepared by analogy with Example 2of European patent 174 464. Synthesis of the compound according to Formula IV is according to the instructions given in European patent 0 222 191 (Example 36).
The optical isomers of azelastin and flezelastin were obtained using the fractional crystallization method. The absolute configuration of azelastin was determined by X-ray structure analysis.